WO2024019519A1 - Pharmaceutical composition, comprising icp-ni, for treating or preventing cytokine storm or inflammatory diseases - Google Patents

Abstract

The present invention relates to a pharmaceutical composition, comprising iCP-NI, for treating or preventing a cytokine storm or inflammatory diseases, which was developed into a patient-friendly inhalation formulation so that a wider variety of patients can use, on their own, the previously developed injectable cytokine storm suppressing community infectious disease treatment, iCP-NI.

Description

Pharmaceutical composition for treatment or prevention of cytokine storm or inflammatory disease comprising iCP-NI

Cross-reference to related applications

This application claims the benefit and priority of Korean Provisional Patent Application Serial No. 10-2022-0088646, filed on July 19, 2022, the entirety of which is incorporated herein by reference.

The present invention relates to a pharmaceutical composition containing iCP-NI for the treatment or prevention of cytokine storm or inflammatory disease, and allows a wider variety of patients to use the previously developed injectable cytokine storm suppressing community infectious disease treatment iCP-NI on their own. To this end, it was developed as a patient-friendly inhalation formulation.

iCP-NI, a treatment for community infectious diseases that suppresses cytokine storm

iCP-NI (improved cell-permeable nuclear import inhibitor) is a community infectious disease treatment substance that is a fusion of a nuclear localization signal (NLS) derived from NF-κB and aMTD, a third-generation hydrophobic cell penetrating peptide (CPP). am. The NLS of iCP-NI increased stability by introducing cysteine at each end of 10 amino acids and connecting them with disulfide bonds to form a ring, and was ultimately composed of 24 amino acids. The NLS of iCP-NI preempts the importin protein, which is essential for inflammation-associated transcription factors (IATFs) when they move into the nucleus, and prevents IATFs from entering the nucleus. This prevents a cytokine storm from occurring in advance. By blocking it, various infectious/inflammatory diseases, including COVID-19, can be treated.

The purpose of the present invention is to develop iCP-NI, a therapeutic agent for suppressing cytokine storms developed as an injectable formulation, into an inhaled formulation so that a wider range of patients can easily access it.

In order to achieve the above object, an example of the present invention is a pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof. provides.

Another example of the present invention is the step of administering to a subject a pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof. Provides a method for preventing or treating a cytokine storm or inflammatory disease comprising a.

This iCP-NI has the effect of suppressing cytokine storm and treating inflammatory diseases.

In addition, the pharmaceutical composition of the present invention can be used as an inhalant, and has excellent effects in reducing the number of neutrophils and macrophages in the affected area, suppressing inflammatory cytokines/chemokines, recovering body weight, and suppressing inflammatory cells and collagen infiltration. represents.

Figure 1 is a graph showing the efficacy of iCP-NI inhalant in suppressing inflammatory cell infiltration in the Poly I:C-induced acute pneumonia model in terms of total cell count (a), neutrophil count (b), and macrophage count (c).

Figure 2 is a photograph verifying the inhibition of inflammatory cell recruitment into the lung by iCP-NI inhalant in the Poly I:C-induced acute pneumonia model using immunofluorescence.

Figure 3. Pro-inflammatory cytokines/chemokines of iCP-NI inhalant in the Poly I:C acute pneumonia model: TNF-α (a), IL-6 (b), and MCP-1 (c) ) and a graph showing the effect of suppressing the expression of IFN-γ (d).

Figure 4. A graph showing the verification of the weight recovery efficacy of iCP-NI inhalant in the Poly I:C induced acute pneumonia model.

Figure 5. Photo showing the long-term protection effect of iCP-NI inhalant in the Poly I:C-induced acute pneumonia model.

Figure 6. Graph showing the weight recovery efficacy of iCP-NI inhalant in SARS-CoV-2.

Figure 7. Photograph of the tissue recovery efficacy of iCP-NI inhalant in SARS-CoV-2.

Figure 8. Graph showing the inhibitory efficacy of iCP-NI inhalant on the cytokines IL-17 (a), TNF-α (b), and IL-1β (c) in SARS-CoV-2.

All technical and scientific terms used in this specification, unless otherwise defined, have the same meaning as commonly understood by experts in the technical field to which the present invention pertains. All publications, patents, and other references mentioned herein are incorporated by reference in their entirety.

Throughout this specification, unless otherwise specified, “include” or “contains” refers to the inclusion of any component (or component) without particular limitation, excluding the addition of other components (or components). cannot be interpreted as

One example of the present invention provides a pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof.

The pharmaceutical composition may include a peptide compound, a stereoisomer thereof, a solvate, or a pharmaceutically acceptable salt as an active ingredient. The pharmaceutical composition may further include known active ingredients with anticancer activity. The pharmaceutical composition may additionally include a pharmaceutically acceptable diluent or carrier. The diluent may be lactose, corn starch, soybean oil, microcrystalline cellulose, or mannitol, and the lubricant may be magnesium stearate, talc, or a combination thereof. The carrier may be an excipient, disintegrant, binder, lubricant, or a combination thereof. The excipient may be microcrystalline cellulose, lactose, low-substituted hydroxycellulose, or a combination thereof. The disintegrant may be calcium carboxymethylcellulose, sodium starch glycolate, calcium monohydrogen phosphate anhydride, or a combination thereof. The binder may be polyvinylpyrrolidone, low-substituted hydroxypropylcellulose, hydroxypropylcellulose, or a combination thereof. The lubricant may be magnesium stearate, silicon dioxide, talc, or a combination thereof.

The pharmaceutical composition may be formulated in the form of oral dosage forms such as powders, granules, tablets, capsules, suspensions, emulsions, syrups, aerosols, external preparations, suppositories, or sterile injection solutions according to conventional methods. When formulated, it can be prepared using diluents or excipients such as commonly used fillers, extenders, binders, wetting agents, disintegrants, and surfactants.

In the pharmaceutical composition, the solid preparation for oral administration may be a tablet, pill, powder, granule, or capsule. The solid preparation may further include excipients. Excipients may be, for example, starch, calcium carbonate, sucrose, lactose, or gelatin. Additionally, the solid preparation may further include a lubricant such as magnesium stearate or talc. In the pharmaceutical composition, the oral liquid preparation may be a suspension, oral solution, emulsion, or syrup. The liquid formulation may contain water or liquid paraffin. The liquid formulation may contain excipients such as wetting agents, sweeteners, flavoring agents, or preservatives. In the pharmaceutical composition, preparations for parenteral administration may be sterilized aqueous solutions, non-aqueous solutions, suspensions, emulsions, freeze-dried products, and suppositories. Non-aqueous solvents or suspensions may contain vegetable oil or ester. The vegetable oil may be, for example, propylene glycol, polyethylene glycol, or olive oil. The ester may be, for example, ethyl oleate. The base of the suppository may be witepsol, macrogol, tween 61, cacao, laurel, or glycerogelatin. The preferred dosage of the pharmaceutical composition varies depending on the individual's condition and weight, degree of disease, drug form, administration route and period, but can be appropriately selected by a person skilled in the art. However, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt may be used in an amount of, for example, about 0.0001 mg/kg to about 100 mg/kg, or about 0.001 mg/kg to about 100 mg/kg. The amount can be divided and administered 1 to 24 times per day, 1 to 7 times per 2 days to 1 week, or 1 to 24 times per month to 12 months. In the pharmaceutical composition, the compound, its isomer, derivative, solvate, or pharmaceutically acceptable salt is present in an amount of about 0.0001% to about 10% by weight, or about 0.001% to about 1% by weight, based on the total weight of the composition. may be included.

As used herein, the terms “administering,” “introducing,” and “implanting” are used interchangeably and are used interchangeably to introduce a composition into an individual by a method or route that results in at least partial localization to the desired site according to one embodiment. It may refer to the arrangement of the composition according to one embodiment of.

Administration can be done by methods known in the art. Administration may be administered directly to the subject by any means, such as, for example, intravenous, intramuscular, oral, transdermal, mucosal, intranasal, intratracheal or subcutaneous administration. You can. The administration may be administered systemically or locally.

The subject may be a mammal, such as a human, cow, horse, pig, dog, sheep, goat, or cat. The subject may be an individual in need of a cytokine storm or inflammatory disease inhibition and/or improvement effect.

The administration of the composition according to one embodiment is 0.1 mg to 1,000 mg, for example, 0.1 mg to 500 mg, 0.1 mg to 100 mg, 0.1 mg to 50 mg, 0.1 mg to 25 mg, 1 mg to 1 mg per day. 1,000 mg, 1 mg to 500 mg, 1 mg to 100 mg, 1 mg to 50 mg, 1 mg to 25 mg, 5 mg to 1,000 mg, 5 mg to 500 mg, 5 mg to 100 mg, 5 mg to 50 mg , 5 mg to 25 mg, 10 mg to 1,000 mg, 10 mg to 500 mg, 10 mg to 100 mg, 10 mg to 50 mg, or 10 mg to 25 mg. However, the dosage may be prescribed in various ways depending on factors such as formulation method, administration method, patient's age, weight, gender, pathological condition, food, administration time, administration route, excretion rate, and reaction sensitivity, and those skilled in the art will Taking these factors into consideration, the dosage can be adjusted appropriately. The frequency of administration can be once a day or two or more times within the range of clinically acceptable side effects, and can be administered at one or two or more locations, daily or at intervals of 2 to 5 days. The number of days of administration can be from 1 to 30 days per treatment. If necessary, the same treatment can be repeated after an appropriate period. For animals other than humans, the dosage per kg is the same as for humans, or the above dosage is converted into, for example, the volume ratio (e.g., average value) of the organs (heart, etc.) between the target animal and human. One dose can be administered.

The composition can be administered intravenous, parenteral, transdermal, subcutaneous, intramuscular, intracranial, intraorbital, intraocular, intraventricular. (intracerebroventricular), intracerebral injection, intracapsular, intrathecal, intracisternal, intraperitoneal, intranasal, intrarectal, intravaginal ( By any one or more methods selected from the group consisting of intravaginal, spraying, oral administration, and dermal application, preferably by one or more methods selected from the group consisting of intravenous, subcutaneous, and dermal application. may be administered.

The composition can be administered intravenous, parenteral, transdermal, subcutaneous, intramuscular, intracranial, intraorbital, intraocular, intraventricular. (intracerebroventricular), intracerebral injection, intracapsular, intrathecal, intracisternal, intraperitoneal, intranasal, intrarectal, intravaginal ( By any one or more methods selected from the group consisting of intravaginal, oral administration, and skin application, preferably by any one or more methods selected from the group consisting of intranasal and oral administration. It may be administered.

The composition may be administered by any one or more methods selected from the group consisting of dry powder inhaler (DPI), metered-dose inhaler, and nebulizer methods.

The cytokine storm or inflammatory diseases include dermatitis, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, fibromyalgia, psoriatic arthritis, Osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, tenosynovitis, peritendinitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, multiple sclerosis, acute and chronic inflammatory diseases, Churg-Strauss syndrome, dermatomyositis, Paget's disease, It may be at least one selected from the group consisting of Alzheimer's disease, cancer or neoplastic disease, viral infectious disease, and lupus, preferably at least one selected from the group consisting of pneumonia, sore throat, tonsillitis, and viral infectious disease.

The viral infectious diseases include influenza; respiratory syncytial virus; HIV; hepatitis B virus; hepatitis C virus; Infection with the SARS-CoV2 virus (COVID-19) or herpes virus, or dengue fever; Or it may be septicemia.

An example of the present invention includes administering to a subject a pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof. Provided is a method for preventing or treating a cytokine storm or inflammatory disease comprising the present invention.

Another example of the present invention provides the use of a composition containing an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof for the prevention or treatment of cytokine storm or inflammatory disease.

Hereinafter, the present invention will be described in more detail through experimental examples and examples. However, these experimental examples and examples are for illustrative purposes only and the scope of the present invention is not limited to these experimental examples and examples.

As used herein, the term “amino acid” in its broadest sense includes naturally occurring L α-amino acids or residues thereof as well as D-amino acids and chemically modified amino acids. For example, amino acids may include mimetics and analogs of the amino acids described above. In the present disclosure, mimetics and analogs may include functional equivalents.

As used herein, the term “prophylaxis” refers to any action that inhibits or delays the development of a cytokine storm or inflammatory disease by administering a composition comprising iCP-NI according to the present invention, and the term “treatment” refers to It refers to all actions in which symptoms of a cytokine storm or inflammatory disease are improved or advantageously modified by administering a composition containing iCP-NI according to the present invention.

As used herein, “administering” means providing a predetermined pharmaceutical composition of the invention to a subject in any suitable manner.

As used herein, the term “subject” refers to any animal, including humans, that has developed or is likely to develop a cytokine storm or inflammatory disease. Animals may include, but are not limited to, humans as well as cattle, horses, sheep, pigs, goats, camels, antelopes, dogs, or cats that require treatment for similar symptoms.

In addition, the routes of administration of the composition according to the present invention include intravenous, parenteral, transdermal, subcutaneous, intramuscular, intracranial, and intraorbital. ), intraocular, intracerebroventricular, intracerebral injection, intracapsular, intrathecal, intracisternal, intraperitoneal, intranasal It can be administered to humans and animals by methods such as intrarectal, intravaginal, spraying, oral administration, and dermal application. Preferably, it can be administered by intravenous, subcutaneous, or dermal application.

The composition of the present invention may further contain auxiliaries such as preservatives, wetting agents, emulsification accelerators, salts and/or buffers for osmotic pressure adjustment, and other therapeutically useful substances, and may be formulated according to conventional methods.

The pharmaceutical composition of the present invention may contain a pharmaceutically acceptable carrier and/or additive. For example, it contains sterile water, physiological saline, common buffers (phosphoric acid, citric acid, other organic acids, etc.), stabilizers, salts, antioxidants (ascorbic acid, etc.), surfactants, suspending agents, isotonic agents, or preservatives. can do. When the pharmaceutical composition according to one embodiment is prepared in a formulation suitable for injection, the recombinant protein may be dissolved in a pharmaceutically acceptable carrier or frozen in a dissolved solution state.

<Example>

Example 1. Preparation of improved cell permeable nuclear transport inhibitor (iCP-NI)

The iCP-NI peptide consisting of the amino acid sequence of SEQ ID NO: 1 according to the present invention uses an advanced macromolecule transduction domain (aMTD) consisting of the amino acid of SEQ ID NO: 2 and the NF-κ nuclear site sequence (NLS) consisting of the amino acid of SEQ ID NO: 3. It was prepared (Table 1).

designation	order	SEQ No.
iCP-NI	IAAVLAAPALVPCVQRKRQKLMPC	SEQ ID NO: 1
aMTD	IAAVLAAPALVP	SEQ ID NO: 2
NLS	CVQRKRQKLMPC	SEQ ID NO: 3

Manufacturing example. Development of inhaled iCP-NI

Inhalation formulations include metered dose inhaler (MDI; Metered Dose Inhaler), which sprays a fixed amount using a propellant gas such as chlorofluorocarbon, dry powder inhaler (DPI; Dry Powder Inhaler), where the patient directly inhales only the active drug powder, and liquid. There are nebulizers that spray and aerosolize drugs into fine particles and allow the patient to inhale them for a relatively long period of time. The inhalation formulation of iCP-NI adopts the nebulizer method and ensures the stability of iCP-NI. Formulation development was completed to create a form suitable for administration. The list of excipients for iCP-NI inhalation formulation is shown in Table 2.

additive	function
iCP-NI	API
NaCl	Tonicifier
Montanox 80	Surfactant
EDTA	Anti-oxidant
Sodium acetate trihydrate	Buffer component
Acetic acid 1mol/L	Buffer component
Purified water type II	Buffer component

Increasing the patient group eligible for administration through the development of inhaled iCP-NI

The previously developed injectable iCP-NI can be administered directly to various inflammatory diseases and applied to various infectious diseases and autoimmune diseases, but due to limitations in the administration method, it has the disadvantage of being difficult to administer to patients who have not visited the hospital. To improve this, a simple administration method using an inhaler was developed so that patients who do not visit the hospital can self-administer the drug, so it can be applied to many patients for whom the existing administration method is difficult.

For example, in the case of COVID-19 that occurred after 2019, the number of infected patients increased explosively and all patients could not be accommodated in hospitals, so most patients underwent home treatment through self-isolation. Injectable formulations are difficult to administer to patients undergoing home treatment. On the other hand, iCP-NI, which was developed as an inhalation formulation, has the advantage of being able to be self-administered not only to critically ill patients in the hospital but also to mildly ill patients receiving treatment at home.

Example 2. dsRNA-simulated Poly I:C-induced acute pneumonia model (Poly I:C-Induced Acute Pneumonitis Model)

To verify the possibility of iCP-NI as a treatment for pneumonia, an acute pneumonia model was constructed using Poly I:C, a compound that mimics viral dsRNA.

When injected into the lungs, dsRNA-mimicking Poly I:C activates TLR7/8 and causes inflammation. This not only induces cytokine activation but also lung inflammation, leading to overall tissue collapse. In this model, iCP-NI can be administered by inhalation to confirm the effective anti-inflammatory effect.

Experimental Example 1. Confirmation of treatment effect in pneumonia model through iCP-NI inhalation

(1) Confirmation of reduction in total cell count, neutrophil count, and macrophage count upon inhalation of iCP-NI

An acute pneumonits model was constructed by intratracheal instilation of Poly I:C, and iCP-NI was inhaled to suppress the infiltration of innate immune cells in bronchoalveolar lavage fluids (BALFs). .

Afterwards, using BALF on day 1 of the Poly I:C-induced acute pneumonia model, the total cell count and changes in neutrophils and macrophages, which are innate immune cells, were measured using flow cytometry. The number was measured. In the diluent group, the total cell number (Figure 1a), neutrophil number (Figure 1b), and macrophage number (Figure 1c) were increased, whereas in the iCP-NI inhalation group, they were all decreased.

Likewise, changes in innate immune cells were confirmed using immunofluorescence using day 1 lung tissue from the Poly I:C-induced acute pneumonia model (Figure 2). In the dilution group, neutrophils (Red) and macrophages (Green) increased between lung tissues, whereas in the iCP-NI inhalation group, they decreased in lung tissues. (Red: Neutrophil marker (Ly6G), Green: Macrophage marker (F4/80), & Blue: Nucleus maker (DAPI))

(2) Confirmation of inflammatory cytokine/chemokine inhibition effect upon iCP-NI inhalation

The effect of iCP-NI inhalation on suppressing the expression of inflammatory cytokines/chemokines in lung lavage fluid was confirmed in the Poly I:C-induced acute pneumonia model.

CBA (cytometric bead array) was analyzed using BALF on day 1 of the Poly I:C-induced acute pneumonia model. As a result of comparison with the dilution group, in the iCP-NI inhalation group, TNF-α was -46.3% (Figure 3a), IL-6 was -32.1% (Figure 3b), MCP-1 was -26.9% (Figure 3c), and IFN- γ decreased by -45.6% (Figure 3d).

(3) Confirmation of weight recovery effect when inhaling iCP-NI

Inhalation of iCP-NI showed a rapid weight recovery effect in the Poly I:C-induced acute pneumonia mouse model (Figure 4).

When the acute pneumonia model was induced with Poly I:C, body weight decreased by -16% on day 1, but body weight began to recover from day 2. Compared to the dilution group, the iCP-NI inhalation group showed increased body weight recovery from the 3rd day, and the largest difference in body weight was observed on the 5th day. Through this, it was confirmed that iCP-NI inhalation was effective in recovering body weight.

(4) Confirmation of the effect of inhibiting inflammatory cells and collagen invasion when inhaling iCP-NI

In a mouse model of Poly I:C-induced acute pneumonia following iCP-NI inhalation, the effect of suppressing lung tissue inflammation and collagen infiltration was confirmed (Figure 5).

When lung inflammation in the mouse model was histologically analyzed on the 7th day after Poly I:C induction, the dilution group had increased inflammatory cell infiltration, tissue collapse, and collagen infiltration between each lung tissue, but the iCP-NI inhalation group had increased inflammatory cell infiltration, tissue collapse, and collagen infiltration between each lung tissue. It was shown that inflammatory cell infiltration, tissue collapse, and collagen infiltration between lung tissues were suppressed.

Experimental Example 2. Confirmation of treatment effect in SARS-CoV2 infection model through iCP-NI inhalation

Looking at the mechanism of SARS-CoV-2, it infects and replicates itself through the ACE2 (angiotensin-converting enzyme 2) receptor on the host's lung and bronchial mucosal cells, which stimulates the entire innate immune system and activates inflammatory transcription factors.

The SARS-CoV-2 infection model is induced by injecting the virus into the nasal cavity of hamsters. In this case, because the severity is not high, weight recovery can also be seen as one of the main indicators.

(1) Confirmation of weight recovery effect when inhaling iCP-NI

For the SARS-CoV-2 infection model, the effect of recovering or increasing body weight of the SARS-CoV-2 model by administering iCP-NI inhalant was confirmed (Figure 6).

As a result of observing body weight changes up to dpi (days post infection) 14 after SARS-CoV-2 infection, weight loss began from dpi 2, and compared to the dilution group, the iCP-NI inhalation group had dpi 3, 4, and 5, 6 All showed that weight loss was suppressed. Through this, the weight recovery effect of iCP-NI inhalation was confirmed.

(2) Confirmation of the effect of suppressing lung tissue damage when inhaling iCP-NI

The inhibitory effect on lung tissue damage was confirmed in a SARS-CoV-2 infected hamster model by administration of iCP-NI.

Lung inflammation was histologically analyzed for each group at 5 and 7 dpi after SARS-CoV-2 infection. At both 5 and 7 dpi, inflammatory cell infiltration increased between each tissue and tissue structure collapsed in the diluted group compared to Mock. On the other hand, in the iCP-NI inhalation group, inflammatory cell infiltration between each tissue was suppressed and the tissue structure was maintained similar to Mock, confirming the tissue recovery effect (Figure 7).

(3) Confirmation of cytokine reduction effect when inhaling iCP-NI

Administration of iCP-NI showed an inhibitory effect on the expression of inflammatory cytokines in lung tissue in a SARS-CoV-2 infected hamster model.

Specifically, when mRNA was extracted from the lungs 5 days after SARS-CoV2 infection and gene expression levels were compared, normalized to Mock and compared with the SARS-CoV-2 model, IL-17 was -58% (Figure 8a). A decrease of -63% in TNF-α (Figure 8b) and -48% in IL-1β (Figure 8c) was confirmed.

Claims (6)

1. A pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof.
2. According to paragraph 1,

   A pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, wherein the composition is administered by one or more methods selected from the group consisting of intranasal and oral administration.
3. According to paragraph 1,

   The composition is used for the treatment of cytokine storm or inflammatory disease, which is administered by one or more methods selected from the group consisting of dry powder inhaler (DPI), metered-dose inhaler, and nebulizer method. Preventive pharmaceutical composition.
4. According to paragraph 1,

   The cytokine storm or inflammatory diseases include dermatitis, conjunctivitis, periodontitis, rhinitis, otitis media, pharyngitis, tonsillitis, pneumonia, gastric ulcer, gastritis, Crohn's disease, colitis, hemorrhoids, gout, ankylosing spondylitis, rheumatic fever, fibromyalgia, psoriatic arthritis, Osteoarthritis, rheumatoid arthritis, periarthritis, tendinitis, tenosynovitis, peritendinitis, myositis, hepatitis, cystitis, nephritis, Sjogren's syndrome, multiple sclerosis, acute and chronic inflammatory diseases, Churg-Strauss syndrome, dermatomyositis, Paget's disease, A pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, which is at least one selected from the group consisting of Alzheimer's disease, cancer or neoplastic disease, viral infection disease, and lupus.
5. According to paragraph 4,

   The viral infectious diseases include influenza; respiratory syncytial virus; HIV; hepatitis B virus; hepatitis C virus; Infection with the SARS-CoV2 virus (COVID-19) or herpes virus, or dengue fever; Or a pharmaceutical composition for the treatment or prevention of cytokine storm or inflammatory disease, which is septicemia.
6. Cytokine storm or inflammatory disease comprising administering to a subject a pharmaceutical composition for the treatment or prevention of a cytokine storm or inflammatory disease comprising an iCP-NI peptide containing the amino acid sequence of SEQ ID NO: 1 and a pharmaceutically acceptable salt thereof. Methods for preventing or treating disease.

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